ArticleResearch square2026
Tissue- and compartment-resolved brain age reveals vascular-metabolic and neurodegenerative aging.
Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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16 authors.
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Abstract
Brain aging reflects heterogeneous vascular-metabolic and neurodegenerative processes, yet brain age is often reduced to a gray matter (GM)-dominant estimate. Emerging evidence suggests that subtle "dirty-appearing" T2-FLAIR abnormalities may mark diffuse white matter (WM) vulnerability that precedes or extends beyond overt WM hyperintensities (WMH). Here we developed a compartment-resolved framework integrating T1-weighted GM features with unthresholded T2-FLAIR WM signal across depth- and lobe-specific surfaces. In 26,446 UK Biobank and 992 ADNI participants, WM brain age captured variation beyond WMH burden and was preferentially associated with cardiometabolic risk before age 65; periventricular WM age statistically linked cardiometabolic burden to cognition. Across the Alzheimer's disease continuum, GM and WM brain age increased with diagnostic severity but showed distinct molecular associations: GM aging aligned more closely with amyloid burden, whereas WM aging showed prominent tau associations. These findings reveal complementary vascular-metabolic and neurodegenerative dimensions of brain aging obscured by global brain age estimates.
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